GROUP 1 Written By: Hesti Retno Budi Arini Rani Youningsih Diah Noorariyani Mu'az Vivian Devi Eka

E. Redy Amukti Yunita Endah Karikasari 125070301111006 125070300111002 125070300111011 125070300111043 125070300111050 125070301111014

Vivi Dian Wahyuningtyas 125070301111031 Ika Dewi Chotijah 125070307111011

DOES FAT CELLS RELATE TO THE INCIDENCE OF HYPERTENSION IN OBESITY

Biomolecular Nutrition year 2013 Supervisor: Dr. Ongko Susetia Totoprajogo MNs, Sp.GK

CHAPTER I INTRODUCTION 1.1 Background of the Study Excess body weight is the sixth most important risk factor contributing to the overall burden of disease worldwide. According to the American Heart Association, one in three Americans, or about 100 million people, has high blood pressure, and nearly 75 million adults are obese. Hypertension and obesity increase the risk of cardiovascular diseases including stroke, heart attack, heart failure, and kidney failure, and obesity promotes diabetes, which also promotes cardiovascular disease. It is estimated that 300,000 deaths annually can be attributed to the cardiovascular complications of obesity.

Obesity and hypertension remain a serious health problem worldwide, in particular in Western societies where the incidence of hypertension and obesity-associated hypertension continues to rise. Compared with the year 2000, the number of adults with hypertension is predicted to increase by 60% to a total of 1.56 billion by the year 2025. The growing prevalence of obesity is increasingly recognized as one of the most important risk factors for the development of hypertension. This epidemic of obesity and obesity-related hypertension is paralleled by an alarming increase in the incidence of diabetes mellitus and chronic kidney disease. This paper examines the evidence linking obesity with hypertension, reviews the mechanisms underlying this link, and discusses the link between obesity and hypertension.

1.2 Identification of the Problem Related to the background of the study, there are some problems that may arise. The writers identifies the problems as follows: a. What is obesity? b. What is hypertension? c. What is fat cell? d. What is cytokines? e. How does fat cells relate to the incidence of hypertension in obesity?

1.3 Purpose a. General purpose That students and readers understand about the relationship between obesity and hypertension. b. Special purpose Describe about obesity and hypertension Explain the effects of obesity for hypertension Explain the relationship between fat cell and hypertension Explain the role of adipose tissue cytokines in metabolic disorders linked to obesity.

CHAPTER II DISCUSSION 2.1 Definition of Obesity Obesity is a disorder that develops from the interaction between genotype and environment and involving social, behavioral, cultural, physiological, metabolic and genetic factors. Several studies have shown that obesity has a negative impact on the health of a population, leading to doctors recommendations has an important function in the management of these conditions and related comorbidities such as hypertension, hyperlipidemia and hyperinsulinemia / insulin resistance. The relationship between obesity and hypertension is common in adults and children. Obese people have higher blood pressure than non -obese individuals. The combination of factors obesity, hypertension and other cardiovascular risk significantly increases the likelihood of adverse cardiovascular outcomes, and increased consideration for aggressive treatment strategies.

2.2 Definition of Hypertension Hypertension is a systolic pressure increasing, the height depending on the age of affected individuals. Blood pressure fluctuates within certain limits, depending on body position, age, and level of stress experienced. Hypertension is also often classified as mild, moderate, or severe based on diastolic pressure. Mild hypertension if the diastolic blood pressure of 95-104, 105-114 diastolic pressure if moderate hypertension, and severe hypertension while diastolic pressure is > 115. Hypertension with systolic pressure increased without an increase in diastolic blood pressure more frequently in the elderly, whereas diastolic hypertension increased pressure without an increase in systolic pressure is more often found in young adults. Hypertension can also be classified as essential or idiopathic, without a specific etiology, the most frequently encountered. If there is cause, is called secondary hypertension.

2.3 Definition of Adipose Some fat cells in the body will form a tissue called adipose tissue. It is becoming increasingly evident that adipose tissue possesses a local RAAS that plays an important role in adipose tissue function. Recent studies suggest that adipose tissue angiotensinogen mRNA expression is higher in abdominal than subcutaneous adipose tissue and therefore maybe associated with increased cardiovascular risk.

Fat cells possess the capability to synthesize all components of the RAAS.They apparently also express Ang II receptors, which make them a target for the paracrineproduced Ang II. That local Ang II maybe a growth factor for fat cells is suggested by experiments in angiotensinogen-knockout(KO) mice that exhibit low blood pressure, have hypotrophic fat cells with reduced fatty acid synthase activity. It has been suggested from studies in these animals that adipose tissue RAAS may govern blood pressure which in other study suggested that blood pressure and sodium homeostasis were restored in the transgenic animals,lending further credence to the theory that an increased fat cell mass may result in higher circulating AGT levels,a nding conrmed in obese individuals. A large number of recent studies have proven that adipose tissue functions as a highly active endocrine organ. Adipose tissues secrete a variety of bioactive substances called adipokines.In obesity,it has been shown that there is an enhanced production of several adipokines (eg,free fatty acids [FFA],angiotensinogen, leptin, resistin,and several inflammatory cytokines,whereas the production of adiponectin, an anti-inflammatory adipokine,is reduced. Leptin Adipocyte derived hormone leptin is a critical mediator of energy balance that provides information on the depletion or accumulation of fat stores to the brain. Although identified as a classic peptide hormones, leptin structure most similar to the cytokine IL - 2. In addition, leptin receptor significantly to the cytokine receptor that the hormone leptin is more precisely identified as a cytokine. Although the role of leptin in the control of energy homeostasis is getting better, but still not clear leptin connection with inflammatory events caused by obesity. The increase in leptin concentrations with body comparable obese. With structures such as leptin that the cytokine IL - 2, leptin plays a role in the inflammatory process. With a high concentration of leptin associated with high-fat diet, so that people who are obese, fat deposits in the body to stimulate the production of the hormone leptin. So with high leptin may be a risk factor for atherosclerosis. 2.4 Definition of Cytokines Cytokines are a class of protein / glycoprotein / soluble polypeptides and produced by lymphocytes and other cells such as macrophages, eosinophils, mast cells and endothelial cells. Cytokines function as intracellular signal that regulates almost all important biological processes such as activation, growth, proliferation, differentiation, cell inflammation, immunity, and defense or tissue morphogenesis.

Cytokines are usually produced by cells in response to stimuli. Cytokines are formed immediately released and not stored in the cell. The same cytokines can be produced by a variety of cells and the cytokines may work against some types of cells and can cause effects through various mechanisms. Various cytokines can have much the same function. Or cytokines can often affect the synthesis or the effects of other cytokines and the effect will appear when bind to specific receptors on the surface of target cells or target cells. Some of these cytokines are IL - 6 and TNF - . 2.4.1 IL - 6 Most of the major functions of cytokines is a paracrine and autocrine factor. IL - 6 is produced by various cells such as lymphocytes, monocytes, fibroblasts and endothelial including macrophages. See the spectrum function in the process of systemic inflammation, IL - 6, are involved in the acute phase of cardiovascular disease. IL - 6 is produced together with IL - 1 and TNF - as the inflammatory response in endothelium and may work together in the process inhibit vasodilation in blood vessels. Analysis of IL - 6 relationship with risk factors for atherosclerosis are very useful for defining the role of cytokines in the mechanism of atherosclerosis in physiological conditions. IL - 6 is one of the inflammatory markers are strongly associated with cardiovascular disease events. This is caused by high levels of IL - 6 in serum is closely related to vascular endothelial dysfunction. Relation to fat metabolism, IL - 6 has a relationship with fat metabolism in which IL 6 can suppress the activity of lipoprotein lipase in adipose tissue that leads to an emphasis on the absorption of triglycerides. This will result in increased levels of fat in the blood that can chronically contribute to the incidence of atherosclerosis. 2.4.2 TNF- Similar with leptin and IL - 6, TNF - plays a role in the inflammatory process. TNF - will be produced when a high fat intake. In this case TNF - will be active in people who are obese, because of the presence of fat deposits TNF - can inhibit fat synthesis. This makes fat accumulate in the blood vessels. In addition, TNF - to inhibit vasodilation in blood vessels. So with the deposition of fat in the blood vessels will lead to atherosclerosis. 2.5 Relations and Events Fat Cells Hypertension in Obesity Obesity is often regarded as a special form of hypertension is not the main cause of primary (essential) hypertension due overweight is regarded as a common cause of primary hypertension. Population studies, for example, have shown that being overweight (as estimated by BMI, waist - hip ratio, abdominal diameter, and other indices) is one of the best predictors for the development of hypertension.

The impact of obesity on hypertension is difficult to assess the cross - sectional studies because the effects of overweight on blood pressure will tend to deteriorate because o obesity continue for many years yet the presence of diabetes mellitus and its complications. A diet high in fatty acids is one of the oxidative stresses that are accepted by all body cells. Everything that could threaten the sustainability of cells or tissue, will responded by inflammatory process. The process of inflammation is the body's response is incurred in order to protect the body, organs, tissues or cells from anything that could cause damage. Inflammatory process induces inflammatory mediators and cytokines. One study showed that the inflammatory process occurs when the body has to consume a diet high in fatty acids. The degree of elevation of levels of IL - 6 levels may be a picture of the inflammatory process that occurs. It means that more and more levels of IL - 6 are formed and the level of inflammation were also heavier, meaning that oxidative stress occurs in the body is also getting heavier.

Briefly, the pathophysiological mechanisms of obesity-related hypertension, as the picture above are some of the things that obesity affects the activation of the renin angiotensin system, increased free fatty acids, cytokines, and ROS (reactive oxygen species). Of RAS activation would lead to hypertension directly through the settings and levels of sodium homeostasis in the kidney. While the increase in free fatty acids, cytokines and ROS cause endothelial dysfunction, impaired function / structure microvascular and microvascular insulin resistance that affects the increase in peripheral resistance, resulting in hypertension. Increase in free fatty acids, cytokines and ROS also cause impaired blood glucose regulation by insulin, causing insulin resistance and hyperinsulinemia induce metabolic activation

stimulates the sympathetic nervous system and hypertension later resulted in activation of the renin- angiotensin system.

Then, how adipose tissue as a collection of fat cells can affect hypertension? Specifically, the fat cells increase in mass as obese will experience a few things: 1. Increased levels of leptin activation of the sympathetic nervous system excess fluid volume and sodium reabsorption in renal hypertension 2. Decreased levels of adiponectin decreased insulin sensitivity endothelial dysfunction
arterial stiffness increase hypertension

3. Increased plasmin activator inhibitor 1 and thromboxane A2 endothelial dysfunction

increased arterial stiffness vasoconstriction hypertension

4. Increased levels of inflammatory cytokines endothelial dysfunction increased arterial stiffness vasoconstriction hypertension 5. Increased levels of free fatty acids inflammation endothelial dysfunction increased arterial stiffness vasoconstriction hypertension, or with a direct effect on the kidneys and lead to hypertension 6. Increased levels of angiotensinogen which affects directly to the kidneys or through the activation of the renin- angiotensin system

CHAPTER III CONCLUSION Incidence of obesity in which a person overweight from too much fat in the body, many referred to as a cause of secondary hypertension. Of many studies related to it, then do further research how the influence of adipose tissue and secretions - which incidentally has increased the incidence of obesity to the incidence of hypertension. Overall, the fat cells which form adipose tissue is associated with the incidence of hypertension in obesity. Its influence is shown through the renin angiotensin system ( RAS ) and endothelial dysfunction either directly to the kidneys or indirectly through the nervous system first.

References

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